A large number of human diseases are now recognized as being autoimmune in nature, yet there is still no clear understanding of what defect(s) of the immune system allows an autoimmune state to develop. One of the most attractive mechanisms postulated as a basis for the development of active autoimmune responsiveness is an imbalance in normal immunoregulatory functions; however, attempts to demonstrate a generalized loss of suppression in human or murine autoimmune disease have provided conflicting results. It is therefore essential to investigate the immune control exerted on a specific autoimmune response itself. An assay for the number of mouse erythrocyte-specific antibody forming cells was developed in order to investigate the cell interactions involved in the development and regulation of an in vitro autoimmune anti-MRBC response. The in vitro response itself will be characterized as to the determinant(s) recognized, the nature of the antibody produced and the cell interactions required. Ly 2+ T cells, shown previously to be suppressive of this in vitro response will be further characterized as to their other surface antigens, specificity and mechanism of action. The origins of, and the inductive influences on the autoresponsive cells and their regulatory cells will be investigated in the kinetics of appearance and disappearance of each interacting cell population in intact animals as well as animals depleted at various stages in ontogeny of B cells or helper T cells. Functional cell populations obtained by positive as well as negative selection procedures from young and old NZB mice as well as non-autoimmune strains of mice will be compared for cellular characteristics and relative activity in the anti-MRBC response. The goal is to identify and characterize mechanisms of control of anti-self responsiveness in normal mice and to identify and characterize cell subsets found in conditions of autoimmunity for any abnormal activities in responses to self antigens.